中国多发性骨髓瘤患者的基因组特征与预后相关性

Genomic characteristics and prognostic correlations in Chinese multiple myeloma patients.

作者信息

Chen Xi, Luo Tianchen, Zhang Wenhui, Wang Sheng, Zhu Mengxuan, He Haiyan, Liu Jin, Lu Jing, Qiang Wanting, Jia Yanchun, Hou Nan, Zhao Xuenan, Zhang Shan, Li Jing, Du Juan

机构信息

Department of Hematology, Myeloma & Lymphoma Center, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, China.

Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.

出版信息

BMC Med Genomics. 2025 Mar 14;18(1):50. doi: 10.1186/s12920-025-02116-5.

DOI:10.1186/s12920-025-02116-5

PMID:40087669

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11907858/

Abstract

BACKGROUND

Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of abnormal clonal plasma cells in the bone marrow. The heterogeneity in Chinese MM populations remains underexplored.

METHODS

We conducted whole-exome sequencing (WES) on 241 tumor samples, complemented by RNA sequencing (RNA-seq) on 131 samples from 212 Chinese MM patients.

RESULTS

We identified a novel mutational signature and analyzed molecular differences between newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients. NFKBIA mutations were notably more frequent in NDMM patients compared to the MMRF-COMMPASS cohort (4/50 vs 22/937, p = 0.048), with additional recurrent mutations in several genes like TTN, IGLL5 and SYNE1. In RRMM patients, UBR5 mutations were more prevalent (4/24 vs 0/50, p = 0.01), alongside frequent mutations in OBSCN, CACNA1H, and HSPG2. Clonal evolution was assessed through multiple time points and locations, identifying genes potentially linked to circulating plasma cell formation. Cox regression analysis revealed that age and mutations in OBSCN and RB1 were significant predictors of progression-free survival (PFS) in NDMM patients. Additionally, albumin, β2-microglobulin, and RB1 mutations were correlated with overall survival (OS).

CONCLUSIONS

In summary, we characterized the genomic landscape of MM in diverse Chinese populations, confirmed clonal evolution, and identified prognostic genes.

摘要

背景

多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征为骨髓中异常克隆浆细胞的增殖。中国MM患者群体的异质性仍未得到充分探索。

方法

我们对241份肿瘤样本进行了全外显子测序（WES），并对来自212例中国MM患者的131份样本进行了RNA测序（RNA-seq）作为补充。

结果

我们鉴定出一种新的突变特征，并分析了新诊断MM（NDMM）患者与复发/难治性MM（RRMM）患者之间的分子差异。与MMRF-COMMPASS队列相比，NDMM患者中NFKBIA突变明显更频繁（4/50 vs 22/937，p = 0.048），其他几个基因如TTN、IGLL5和SYNE1也存在复发性突变。在RRMM患者中，UBR5突变更为普遍（4/24 vs 0/50，p = 0.01），同时OBSCN、CACNA1H和HSPG2也频繁发生突变。通过多个时间点和部位评估克隆进化，确定了可能与循环浆细胞形成相关的基因。Cox回归分析显示，年龄以及OBSCN和RB1突变是NDMM患者无进展生存期（PFS）的显著预测指标。此外，白蛋白、β2-微球蛋白和RB1突变与总生存期（OS）相关。